The IDH2 Knockout PaTu 8988t Polyclonal Cells product consists of a CRISPR/Cas9-edited polyclonal population derived from the human pancreatic ductal adenocarcinoma cell line PaTu 8988t, harboring a targeted disruption of the IDH2 gene. This genetically heterogeneous pool allows researchers to study loss-of-function effects in a population context, mirroring the complexity of tumor cell heterogeneity. The product is supplied as a growing culture and is intended for in vitro research applications in cancer metabolism and redox biology. This knockout model provides a versatile tool for interrogating IDH2-dependent processes in pancreatic cancer metabolism and redox homeostasis.
PaTu 8988t is an epithelial cell line originally established from a liver metastasis of a human pancreatic ductal adenocarcinoma. It is widely employed as a model system to investigate the molecular mechanisms underlying pancreatic cancer metastasis and acquired drug resistance. The line retains characteristic features of aggressive pancreatic cancer, including metastatic potential and altered metabolic dependencies, making it particularly suitable for dissecting metabolic adaptations that support tumor progression and therapeutic evasion.
IDH2 encodes mitochondrial isocitrate dehydrogenase 2, which catalyzes the NADP+-dependent oxidative decarboxylation of isocitrate to ??-ketoglutarate (??-KG), generating NADPH. This reaction is central to the TCA cycle, glutamine metabolism, and redox homeostasis. IDH2 is transcriptionally regulated by c-Myc and HIF-1??, downstream of the PI3K/AKT pathway, and modulated by FOXO3a. The produced ??-KG is a co-substrate for TET dioxygenases, JmjC histone demethylases, and prolyl hydroxylases, linking metabolism to epigenetics and hypoxic response. IDH2 functions as a homodimer requiring NADP+ and Mg2+ or Mn2+ ions.
In the PaTu 8988t pancreatic cancer context, disruption of IDH2 ablates a critical source of mitochondrial NADPH, sensitizing cells to oxidative stress and impairing reductive biosynthesis. Loss of IDH2-mediated ??-KG production may also perturb the activity of ??-KG-dependent dioxygenases, with consequences for DNA and histone demethylation dynamics. Accordingly, this polyclonal knockout population provides a physiologically relevant platform to dissect how IDH2-dependent metabolic and epigenetic networks influence pancreatic cancer cell proliferation under nutrient-limited or chemotherapeutic stress, thereby offering insights into the metabolic vulnerabilities of metastatic pancreatic tumors.
This IDH2 knockout model supports a broad spectrum of advanced applications. It is ideal for pancreatic cancer metabolism research, redox homeostasis studies, synthetic lethality screening in conjunction with metabolic inhibitors (e.g., glutaminase or fatty acid oxidation blockers), and drug sensitivity assays involving gemcitabine or other standard-of-care agents. Researchers can validate knockout status via Western blotting and RT-qPCR, assess functional consequences by measuring intracellular ??-KG and NADPH levels or IDH2 enzymatic activity, and monitor metabolic reprogramming through Seahorse flux analysis. Proliferation can be quantified by crystal violet assays, and oxidative stress can be evaluated using ROS detection probes. These tools enable systematic interrogation of IDH2-dependent vulnerabilities in pancreatic cancer. For additional details or customized solutions, please contact Ascent Research.
